This application addresses broad Challenge Area 06 - Enabling Technologies - and specific Challenge Topic, 06-DA-104: Development of new technologies to change patient and provider behaviors to improve adherence. Since the advent of highly active antiretroviral therapy (HAART), significant numbers of HIV-positive individuals are living prolonged and healthier lives (O'Cleirigh and Safren, 2008;Safren et al., 2001;2009). HAART, which typically involves a combination of medications, leads to reductions in viral load, greater immune system function, and less likelihood of clinical immune deficiency in patients with HIV infection (Carpenter et al., 1997;Flexner, 1998;Goebel, 1995). However, HAART effectiveness is wholly dependent on complete adherence to prescribed medication regimens, which often involve different dosing schedules and food intake conditions, requiring adherence to a complex and frequently confusing combination of medications throughout an indefinite course of treatment. Drug use has been shown to severely erode adherence (Hinkin et al., 2007), and because adherence can be further threatened by stress and negative mood states, recent recommendations have underscored the importance of developing adherence interventions that also address stress, mood states and substance use (Scott-Sheldon, 2008;O'Cleirigh and Safren, 2008;Safren et al., 2009). A meta-analysis of studies of stress management interventions for HIV-positive people found evidence for their effectiveness in reducing stress (Scott-Sheldon et al., 2008). Recently, in further recognition of the link between emotional states and medication adherence, Safren and associates (2009) conducted a randomized controlled trial of a medication adherence intervention for HIV-positive individuals diagnosed with depression and found positive effects on both medication adherence and depression. Therefore, it seems clear that efficacious interventions to improve adherence to HIV medications are available, and that providing training in medication adherence strategies within the framework of stress and mood management could be an effective approach for improving both mood states and medication adherence. However, all the HIV medication adherence programs created to date require professional staff, trained specifically in the adherence procedures, to interact in person with the patients over the course of multiple sessions. In partnership with the Whitman Walker Clinic, we propose to conduct a randomized controlled trial of a web-based medication adherence program for HIV-positive individuals presented within the framework of a stress and mood management program. The randomized trial will be conducted over a two-year period with a sample of 200 patients of the Whitman Walker Clinic, assessing adherence mainly with the electronic Medication Event Monitoring Systems (MEMS), along with multiple self-report assessments of stress, mood and drug use. The Whitman Walker Clinic is located in Washington, DC, where a large proportion of the HIV- positive population is comprised of recent or current drug users. If shown effective, the web-based SMM-AD program would be available to all HIV-positive people with access to the Internet, greatly expanding the reach of medication adherence programs. Drs. Cook and Billings (PI and Co-Investigator) have successfully created and tested several web- based behavioral health programs, including the Stress and Mood Management (which includes a segment on substance use), recently shown efficacious in a randomized controlled trial (Cook et al., 2007;Billings et al., 2008). They are currently conducting a randomized trial of a web-based HIV prevention program for women. Steven Safren, who has developed and tested multiple HIV medication adherence programs, and David Murray, a recognized expert on the design and analysis of randomized trials, will serve as consultants to the project. PUBLIC HEALTH RELEVANCE: Since the advent of highly active antiretroviral therapy (HAART), significant numbers of HIV-positive individuals are living prolonged and healthier lives. However, HAART effectiveness is wholly dependent on complete adherence to a complex and frequently confusing combination of medications throughout an indefinite course of treatment. Drug use, stress, and negative mood states can further lower rates of HIV medication compliance. Recent data suggests, however, that in-person depression and medication adherence treatment can improve mood and increase medication compliance. Unfortunately, the reach of in-person interventions is limited by their cost and relative inaccessibility. The outcome of this research project will be a comprehensive, innovative, web-based medication adherence program for HIV-positive individuals presented within the framework of a stress and mood management program. This will greatly expand access to an effective medication adherence program, thereby improving the physical and mental health of those infected with HIV.